Mild Thrombocytopenia Research Articles

Characterization of Thrombocytopenia in Pediatric Patients in Noncritical Hospital Setting: An Institutional Review From Pakistan

Pediatric thrombocytopenia is frequently observed in critical care and oncology settings with an increased risk of bleeding and platelet transfusions. However, little is known about low platelets in childhood during seasonal influence. This study aimed to evaluate the frequency and severity of pediatric thrombocytopenia in the postflood period. The patients aged 1 to 18 years with thrombocytopenia (platelet count <150×109/L) were studied from August to December 2022 after institutional ethical approval (ERC-Path-2022-8044-23395). Data was collected from electronic health records and laboratory information systems. Of 2318 admitted patients, 192 (8.3%) including 128 males and 64 females had thrombocytopenia. The median (IQR) age was 12 (8 to 15) years. Mild, moderate, and severe thrombocytopenia were seen in 109 (56.8%), 76 (39.5%), and 7 (3.6%) patients, respectively. Concomitant leucopenia was observed in 77 of 192 patients (40.1%). Infection was the predominant cause of low platelets (N=175 or 91.1%). Only 15 patients (7.8%) had grade 1/2 bleeding. Overall, 176 patients (92%) were discharged in stable conditions and no mortality was observed. The frequency of pediatric thrombocytopenia in the noncritical and nononcological care settings was <10% and mostly observed in association with underlying infections. The frequency of bleeding manifestation and platelet transfusions was minimal in this group.

Detection of DNA of Leishmania infantum in the brains of dogs without neurological signs in an endemic region for leishmaniasis in the state of Rio Grande do Sul, Brazil.

Canine visceral leishmaniasis (CVL) is a parasitic disease caused by the protozoan Leishmania infantum. Neurological infection occurs due to the parasite's ability to cross the blood-brain barrier. It is known that dogs can remain infected with a subclinical infection for life, potentially acting as reservoirs for L. infantum when bitten by sandflies. In this context, the objective of this study was to evaluate the occurrence of Leishmania spp. in the brains of dogs from the metropolitan region of Rio Grande do Sul, Brazil, without a history of neurological disease but residing in an endemic area for L. infantum. A total of 200 samples, from 2022 to 2023, were evaluated using conventional Polymerase Chain Reaction (PCR) with the primers Leishmini-F GGKAGGGGCGTTCTGC and Leishmini-R STATWTTACACCAACCCC, aiming to amplify a product of 120 base pairs for Leishmania spp. To identify the species, a multiplex PCR was used, differentiating L. braziliensis (127bp), L. amazonensis (100bp), and L. infantum (60bp), with the molecular target being the conserved region of the kinetoplast DNA (kDNA) minicircle, specific to Leishmania spp. Of the 200 samples evaluated, 26.5% (53/200) tested positive in the conventional PCR reaction for Leishmania spp., with the PCR multiplex the only species detected was Leishmania infantum. The average age of the positive animals was 5.08years, with 47.2% being females and 52.8% being males; among these, mixed-breed dogs were the most predominant, representing 43.4% of the total. Clinical signs varied: hepatomegaly in two dogs, pronounced neutrophilic hepatitis in one, splenomegaly in one with lymphoid hyperplasia, and glomerulonephritis and nephritis in two animals. Mild anemia and thrombocytopenia were found in eight, with pale mucous membranes in three, and diffuse alveolar edema in one case. Notable pathological findings included suspected distemper in one animal and lymphoplasmacytic meningitis in another. Histopathological findings revealed alveolar edema and acute renal failure. A third dog exhibited bilateral hydrocephalus and diffuse edema in the brain. Additional changes, such as mild inflammatory infiltrate and slight vacuolar degeneration, were observed in 11.3% of the analyzed brains. There was no clinical suspicion of leishmaniasis in any of the studied cases. Therefore, the detection of L. infantum DNA in the brains of dogs suggests that animals with subclinical infection may play a crucial role in the spread of leishmaniasis, and infection by Leishmania spp. should be considered as a differential diagnosis for neurological disease in endemic areas for the protozoan.

LMAN1 serves as a cargo receptor for thrombopoietin.

Thrombopoietin (TPO) is a plasma glycoprotein that binds its receptor on megakaryocytes (MK) and MK progenitors, resulting in enhanced platelet production. The mechanism by which TPO is secreted from hepatocytes remains poorly understood. LMAN1 and MCFD2 form a complex at the endoplasmic reticulum membrane, recruiting cargo proteins into COPII vesicles for secretion. In this study, we showed that LMAN1 deficient mice (with complete germline LMAN1 deficiency) exhibited mild thrombocytopenia, whereas the platelet count was entirely normal in mice with approximately 7% Lman1 expression. Surprisingly, mice deleted for Mcfd2 did not exhibit thrombocytopenia. Analysis of peripheral blood from LMAN1 deficient mice demonstrated normal platelet size and normal morphology of dense and alpha granules. LMAN1 deficient mice exhibited a trend toward reduced MK and MK progenitors in the bone marrow. We next showed that hepatocyte-specific but not hematopoietic Lman1 deletion results in thrombocytopenia, with plasma TPO level reduced in LMAN1 deficient mice, despite normal Tpo mRNA levels in LMAN1 deficient livers. TPO and LMAN1 interacted by co-immunoprecipitation in a heterologous cell line and TPO accumulated intracellularly in LMAN1 deleted cells. Altogether, these studies confirmed the hepatocyte as the cell of origin for TPO production in vivo and were consistent with LMAN1 as the endoplasmic reticulum cargo receptor that mediates the efficient secretion of TPO. To our knowledge, TPO is the first example of an LMAN1-dependent cargo that is independent of MCFD2.

Implementation of Primary Immune Thrombocytopenia Clinical Practice Guidelines for Management of Pregnancy.

Background: Managing primary immune thrombocytopenia (ITP) in pregnancy is challenging. Providers must balance bleeding risk against medication toxicity. The evaluation of the implementation of pregnancy-specific ITP clinical guidelines has not been widely studied. The goal of this study was to describe the implementation of pregnancy-specific ITP guidelines at an academic health center. Methods: We conducted a retrospective chart review at the University of Oklahoma Health system from 2011 to 2020. Descriptive statistics were calculated to summarize the characteristics of the study population. Management, according to the clinical guidelines (American Society of Hematology; American College of Obstetricians and Gynecologists) was evaluated during pregnancy and during/for delivery. Results: A total of 85 pregnant persons with ITP were included. The majority (68%; 58/85) delivered vaginally. There were 0 maternal deaths and 2 infant deaths. No patients had major bleeding during pregnancy. Postpartum hemorrhage was experienced by 14%. The management of thrombocytopenia during pregnancy was 100% adherent to the strong recommendation for severe (n = 13) and mild (n = 11) thrombocytopenia. However, 18/50 (36%) asymptomatic persons with moderate thrombocytopenia received treatment despite the strong recommendation that treatment was unnecessary. Additionally, 8/21 (38%) persons with moderate thrombocytopenia received treatment to increase platelet counts for epidural anesthesia despite the guideline's suggestion that it was unnecessary. Conclusions: During pregnancy, patients with severe thrombocytopenia (i.e., most at risk of bleeding) received treatment. On the other hand, approximately 40% of pregnant persons with ITP received unnecessary treatment for moderate asymptomatic thrombocytopenia either during pregnancy or for an epidural. Utilizing clinical practice guidelines would reduce the overtreatment of pregnant persons which would reduce the potential side effects of therapy for the mother and infant.

Risk of thromboembolic and haemorrhagic events associated with anticoagulation among 11,355 patients with non-valvular atrial fibrillation and thrombocytopenia

Abstract Background Oral anticoagulation (OAC) is the mainstay for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Management is challenging among patients with NVAF complicated with thrombocytopenia. Purpose We compared risk of thromboembolic and hemorrhagic events between vitamin-k antagonist (VKA) and direct oral anticoagulants (DOAC) users. Methods We retrospectively analyzed patients with thrombocytopenia and NVAF prescribed VKA (N=5,251, 46.2%) and DOAC (N=6,104, 53.8%) between January 2012 and July 2022 in 16 public hospitals in Hong Kong. Mild to moderate thrombocytopenia was defined as mean platelet count (PLT) 100-150 × 10^9/L and 50-100 × 10^9/L respectively, during the year of OAC initiation. Propensity-matched cohorts of VKA and DOAC were generated on the basis of age, sex, baseline co-morbidities (components of CHA2DS2VASC and HAS-BLED scores) and medications. Time to intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB) and ischemic stroke (IS) was analyzed using competing risk regression, accounting for death as competing risk. Subgroup analysis was performed to detect heterogeneity of effect across mild and moderate thrombocytopenia. Secondary outcome included (i) comparisons between 4 DOAC agents with full dose; (ii) Full-dose DOAC vs. reduced-dose DOAC. Results Of the whole cohort (N=11,355, mean age 75.8±10.5, female 38.6%), 10.3% (n=1,174) and 89.7% (n=10,181) had moderate and mild thrombocytopenia, respectively. After propensity-score matching, VKA and DOAC (n=4,302 each cohort) users were well balanced at baseline characteristics, with a median follow-up of 4.0 (IQR: 1.6-7.3) years. Overall, utilization of DOAC was associated with reduced risk of ICH [Hazards Ratio (HR) 0.56 (95% CI 0.45-0.70)] and GIB [HR 0.60 (95% CI 0.48-0.75)], compared with VKA. No difference in risk of IS was observed [HR 1.00 (95%CI 0.83-1.20)]. Dosing reduction of DOAC made no difference in all outcomes. Subgroup analysis demonstrated the benefit in decreasing GIB might be more marked in moderate thrombocytopenia [(HR 0.24 (95%CI 0.09-0.61)], than in mild thrombocytopenia [HR 0.64 (95%CI 0.51-0.81)]. Conclusion In patients with NVAF and thrombocytopenia, DOAC has similar efficacy but better safety profile than VKA. In terms of GIB, the superiority appeared to be more pronounced in patients with more significant thrombocytopenia.

Association of ticagrelor vs clopidogrel with net adverse clinical events in NSTEMI patients with mild thrombocytopenia

Abstract Backgrounds: Guidelines currently recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (ADPT) for non-ST-elevation myocardial infarction (NSTEMI). However, there are no established recommendations for managing NSTEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in NSTEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using data from the Health and Medical Big Data Super Platform from January 2010 to June 2023. The study included NSTEMI patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (eithor clopidogrel or ticagrelor). Patients were followed up for at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was used to balance the observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included cardiac death, recurrent myocardial infarction and, ischemic stroke. Results The study cohort comprised 2969 participants, with a median age of 72 years and 29.2.0% female. After adjustment using inverse probability of treatment weighting, ticagrelor and clopidogrel showed similar rates of NACE (aHR, 0.84; 95%Cl, 0.58-1.21). Cardiac death (aHR, 0.99; 95%Cl, 0.54-1.83) and ischemic stroke (aHR, 0.94; 95%Cl, 0.49-1.81) did not significantly differ between the two groups. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction (aHR, 0.44; 95%Cl, 0.21-0.93). Conclusion In routine clinical practice, among NSTEMI patients with a platelet count of 100~150×109/L, ticagrelor, did not showed a significant difference in the risk of NACE at 1 year compared with clopidogrel. However, ticagrelor was associated with a lower rate of recurrent myocardial infarction. Further research is warranted to confirm the this conclusion.

Association of ticagrelor vs clopidogrel with net adverse clinical events in STEMI patients with mild thrombocytopenia

Abstract Backgrounds Current guidelines advocate for aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing STEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in STEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023.The study included STEMI-patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (either clopidogrel or ticagrelor) All STEMI patients with a platelet count of 100~150×109/L were included in the analysis with a follow-up of at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was utilized to balance observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, including ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes were cardiac death, recurrent myocardial infarction, and ischaemic stroke. Results The study cohort consisted 2941 participants with median age of 69 years, and 21.0% were female. Following adjustment using the inverse probability of treatment weighting, ticagrelor and clopidogrel demonstrated similar NACE (aHR, 0.86; 95%CI, 0.60-1.23). Cardiac death (aHR, 0.69; 95%CI, 0.36-1.31), recurrent myocardial infarction (aHR, 0.94; 95%CI, 0.50-1.78), and ischaemic stroke (aHR, 0.62; 95%CI, 0.34-1.14) did not significantly differ between the two groups. Conclusion In routine clinical practice, among STEMI patients with a platelet count of 100~150×109/L ticagrelor compared with clopidogrel, was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this particular patient population.

Association of ticagrelor vs clopidogrel with net adverse clinical events in patients with mild thrombocytopenia undergoing PCI

Abstract Backgrounds Current guidelines recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for managing ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L, undergoing percutaneous coronary intervention (PCI). Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events for patients with mild thrombocytopenia undergoing PCI. Methods A retrospective cohort study of patients with mild thrombocytopenia undergoing PCI who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (includinig clopidogrel or ticagrelor) was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023. All patients meeting the criteria were included in the analysis, with a follow-up of at least one year. Propensity Score Matching (PSM) was performed to equalize the effects of following characteristics: age, sex, hypertension, diabetes, dyslipidemia, stroke, atrial fibrillation, Killip class, percutaneous coronary intervention (PCI), beta-blockers, statins, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB), angiotensin receptor-neprilysin inhibitor (ARNI), diuretic, organic nitrates, and oral anticoagulation. The primary endpoint was net adverse clinical events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included the components of NACE. Results A total of 3647 patients met the inclusion criteria, with 2684 receiving aspirin plus clopidogrel and 963 receiving aspirin plus ticagrelor, matched by a 1:3 ratio using the PSM method. Demographic characteristics were well balanced between the clopidogrel and ticagrelor groups. The 1-year risk of NACE did not significantly differ between ticagrelor and clopidogrel (11.1% vs. 8.4%, p=0.370). Similarly, there was no significant difference in the risk of cardiac death (7.3% vs. 4.2%, p=0.720), recurrent myocardial infarction (9.3% vs. 5.8%, p=0.550), ischemic stroke (8.8% vs. 6.7%, p=0.055), or BARC type ≥ 3 bleeding (7.9% vs. 4.5%, p=0.990). Conclusion In routine clinical practice, among patients with a platelet count of 100~150×109/L undergoing PCI, ticagrelor compared with clopidogrel was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this setting, considering potential unmeasured confounders.

Thrombocytopenia as a Prognostic Marker in Patients with Acute Encephalitis at a Tertiary Care Center in Northern India.

Acute encephalitis (AE) is associated with a high burden of mortality and permanent disability and has a spectrum of underlying etiologies. The prognosis of encephalitis is difficult and almost all the patients seem to be at a high risk of poor outcomes. A number of physiological changes take place during encephalitis and have been evaluated for their prognostic value. Platelet count, which has been recognized as a surrogate prognostic marker in various viral illnesses, has recently been recognized to have a prognostic value in AE too. In the present study, we attempted to study the role of thrombocytopenia in the prognosis of AE. Total of 98 cases based on clinical, cerebrospinal fluid, and radiological profiles consistent with the diagnosis of AE were enrolled in the study. A clinical profile was noted, and platelet count was assessed. Thrombocytopenia was defined as platelet count <150,000/mm3. Platelet count 100,000-150,000, 50,000-99,999, and <50,000/mm3 were considered mild, moderate, and severe thrombocytopenia. The underlying etiology was explored, and patients were followed till discharge/outcome. The outcome was noted in terms of the Modified Rankin score (MRS). MRS 0-2 was considered good, 3-4 fair, and 5-6 as poor outcome. The mean age of patients was 34.06 ± 18.76 years. Majority of patients were women (54.1%). Prevalence of thrombocytopenia was 75.5%. A total of 34 (45.9%) had mild, 30 (40.5%) had moderate, and 10 (13.5%) had severe thrombocytopenia. Acute viral encephalitis (unclassified) was the most common etiology (33.7%), followed by scrub meningoencephalitis (24.5%) and Japanese encephalitis (12.2%), respectively. Good, fair, and poor outcomes were noted in 48 (49%), 21 (21.4%), and 29 (29.6%) cases. On univariate analysis, no significant association of poor outcome was seen with age, sex, duration of fever, and mechanical ventilation need (P > 0.05). Low Glasgow Coma Scale (GCS), splenomegaly, low platelet count, and Japanese encephalitis virus/scrub typhus etiologies were found to be significantly associated with poor outcomes (P < 0.05). Thrombocytopenia compared to normal platelet count and severe thrombocytopenia compared to mild and moderate thrombocytopenia were significantly associated with poor outcomes (P < 0.05). On multivariate analysis, GCS <8 (odds ratio [OR] =4.52; 95% confidence interval [CI] =1.56-13.20) and thrombocytopenia (OR = 11.92; 95% CI = 1.38-103.32) emerged as independent predictors of poor outcome. The findings of the study showed that low GCS and thrombocytopenia could be used as predictors of poor outcomes in AE cases.

Neonatal Alloimmune Thrombocytopenia with HLA and HPA-3a Antibodies in a Down Syndrome Neonate

Abstract Introduction/Objective Neonatal Alloimmune Thrombocytopenia (NAIT) is a rare cause of thrombocytopenia seen in 1 in 11,000 neonates with lethal risks such as intracranial hemorrhage. This is caused by maternal antibodies against fetal platelets and the most common culprits are antibodies to Human Platelet Antigen-1b (HPA-1b) but rarely to Human Leukocyte Antigen (HLA) antibodies. We describe a rare case of a newborn with Down syndrome with maternal antibodies against HLA and presumed antibodies against HPA-3a. Down syndrome causes hematologic abnormalities with mild thrombocytopenia. Methods/Case Report A preterm male with Down syndrome was born via Cesarean delivery due to non-reassuring fetal heart tracing at a gestational age of 35 weeks. He was admitted for low birth weight and his hospital course was complicated by severe thrombocytopenia of 37 x 10^9/L without bleeding symptoms. Initially attributed to his trisomy 21 but due to his suboptimal response to platelet transfusion, NAIT was suspected. The mother had antibodies against HLA on initial screen and was presumed to have HPA-3a antibodies since she was homozygous for HPA-3b antigen. The neonate was managed with multiple transfusions of platelets and Intravenous Immunoglobulin (IVIG). The platelet count stabilized to 325 x 10^9/L on his 25th day of life. Results (if a Case Study enter NA) n/a Conclusion To our knowledge, this is the only published case of NAIT with both HPA-3a and HLA antibodies in a Down syndrome neonate. It is unclear whether the primary reason for thrombocytopenia is due to NAIT caused by HPA-3a antibodies or HLA antibodies or his existing Down syndrome. This case contributes to understanding the complexity between immune-related diseases such as NAIT and genetic conditions such as Down syndrome. Although NAIT occurs rarely, timely diagnosis and treatment is of utmost importance to prevent lethal complications.

Two Concurrent Cases of NAIT in Pregnant Sisters

Abstract Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal antibodies directed against fetal platelet antigens inherited from the father. Approximately 80% of cases of NAIT are attributed to antibodies against human platelet antigen (HPA)-1a and less commonly to antibodies against HPA-5b. We present two cases of possible NAIT attributed to anti-HPA-5b that were identified in sisters requiring concurrent management. Patient #1 is a 32-year-old G9P4044 woman with one pregnancy complicated by intrauterine growth retardation and partial placental abruption, another pregnancy complicated by fetal anomaly (intracerebral hemorrhage) status post termination of pregnancy at 23 weeks’ gestation and three miscarriages (one with chromosomal abnormality). The patient is homozygous for HPA-1a and HPA-5a, and the partner is homozygous for HPA-5b. HPA-5b antibodies and HLA antibodies were identified in the patient’s serum. Deemed at high risk for subsequent NAIT, she was started on intravenous immunoglobulin twice weekly and steroids during her second trimester until delivery. The patient underwent weekly fetal sonograms during pregnancy which were normal. The patient’s platelet counts were stable. The patient refused caesarean delivery. At 38 weeks’ gestation, the patient gave birth to a healthy female via normal spontaneous vaginal delivery. HPA-5b negative platelets were procured from our blood supplier, but neither the mother nor neonate required transfusion. The neonate showed no signs of bleeding and had normal platelet counts. Ultrasound imaging of the head was unremarkable. The patient and neonate were discharged home. Patient #2 is a 33-year-old G13P6156 woman with a prior pregnancy complicated by stillbirth at 32 weeks’ gestation. Considering her personal and family history, HPA testing was performed and HPA-5b antibodies were identified in the patient’s serum. The patient’s partner is heterozygous for HPA-5b. Crossmatched platelets were procured from our blood supplier. The patient refused caesarean delivery. The patient gave birth at 37 weeks’ gestation to a healthy male via normal spontaneous vaginal delivery. The fetus had mild thrombocytopenia (107 x 103/uL), with no bleeding or bruising identified. Neither the mother nor neonate required transfusion. The patient and neonate were discharged home. Ultrasound imaging of the head was unremarkable, and his thrombocytopenia resolved. While some studies postulate that anti-HPA-5b identification may be coincidental rather contributory to the disease process, these cases re-emphasize the importance of obtaining pregnancy, neonatal and family history to best risk stratify patients and determine management from both the clinical and transfusion medicine perspectives. If transfusion is needed, transfusion options include HPA negative platelets, crossmatched platelets and random donor platelets depending on clinical urgency and platelet availability.

A Study of Clinical, Hematological and Biochemical Profiles of Patients with Pancytopenia

This study aimed to investigate patients’ clinical, hematologic, and biochemical profiles with pancytopenia. This prospective observational study was conducted at a tertiary care hospital from January 2019 to June 2020 on 80 patients, 39 (48.7%) were males and 41 (51.2%) were females, over the age of 18 presenting with pancytopenia. All the patients were subjected to thorough clinical and physical examinations. A complete blood count (CBC), peripheral smear examination, bone marrow aspiration, and reticulocyte count were performed. The data was analyzed using the IBM SPSS 20.0 software. Most of the cases had moderate (Hb&lt;7-9.9g/dl) anemia (63.7%, 51/80 cases), while severe anemia (&lt;7g/dl) was seen in 31.2% (25/80) cases, and 5% (04/80) cases showed mild anemia (Hb&lt;10-11.9g/dl). Most patients with severe anemia had vitamin B12 deficiency anemia (12/80), that is, 15%. Macrocytic anemia was noted in preponderance (50% cases, 40/80), whereas microcytic hypochromic and normocytic hypochromic anemia constituted 21.3% (17/80), and dimorphic anemia was seen in 7.5% (06/80) cases. Based on WBC counts, 56.3% of cases (45/80) showed counts between 2000 and 4000 cells/cu.mm, while counts between 1000 and 2000 cells/cu.mm were seen in 31.3% of cases (25/80), and 12.5% of cases (10/80) had counts of &lt;1000 cells/cu.mm. The study highlighted that 28.8% (23/80) had a platelet count between 50,000 and 1 lakh/cu.mm (mild thrombocytopenia), 36.3% (29/80) cases had a platelet count between 20,000 and 50,000/cu.mm (moderate thrombocytopenia), and 35% (28/80) cases had a platelet count less than 20,000/cu.mm (severe thrombocytopenia). The most common diagnosis of bone marrow aspiration was megaloblastic anemia, seen in 50.0% (6/12) cases. Megaloblasts were seen in 50.0% (6/12) cases of megaloblast anemia. The bone marrow aspirate of a patient with dengue fever and malaria showed macrophages containing engulfed red blood cells, lymphocytes, and platelets. Myeloblasts (&gt;20%) were seen in 1 (8.3%) case of AML, and decreased myelopoiesis was seen in 25% of cases (two cases of aplastic anemia and one case of MDS). This study concludes that vitamin B12 deficiency is the most common cause, which is more common in people who are strict vegetarians, with a predominance in the younger age group. The study also emphasized the vitality of the physical findings, detailed primary hematologic and biochemical investigations, and peripheral blood pictures, all of which provide precious information in the work-up of pancytopenia patients.

THROMBOCYTOPENIA IN NEONATES: INCIDENCE, PRESENTATION, AND STUDY OF CORRELATED FACTORS AT A LAHORE TEACHING HOSPITAL

Background: Patients with thrombocytopenia have been observed to experience changes in their coagulation profile and severity of disease. This study aims to see the incidence, presentation, and correlating factors of thrombocytopenia in newborns. Methods: From Jan 2023 to Jan 2024, 200 newborns in the Paediatric and Pathology Departments of Chaudhry Muhammad Akram Teaching and Research Hospital participated in a cross-sectional study. Utilizing SPSS-23, overall data was analysed. Results: In this study 138 (69%) of the 200 newborns were female, and 62 (31%), were male. Seventy-six (38%) neonates had thrombocytopenia, whereas 124 (62%), neonates had normal platelet counts. Of the 76 newborns, 42 (21%) had mild thrombocytopenia, 25 (12.5%) had moderate thrombocytopenia, and 9 (4.5%) had severe thrombocytopenia. Thirty-five percent early-onset neonatal thrombocytopenia (EOT) had early onset thrombocytopenia, while 46 (23%) had thrombocytopenia in the late onset (LOT) phase. There was a strong correlation discovered between thrombocytopenia and anaemia, jaundice asphyxia, low birth weight, preterm and full-term neonatal birth, and neonatal jaundice. The correlation of bleeding in neonates with thrombocytopenia was significant (p&gt;0.05). Conclusion: Moderate to severe thrombocytopenia in newborns often follows mild thrombocytopenia. Thrombocytopenia is highly correlated with bleeding, preterm birth, full-term birth (extensive monitoring during childbirth), anaemia, hypoxia, and sepsis. In sick newborns, severe thrombocytopenia is considered as a prognostic marker. Pak J Physiol 2024;20(3):37–9, DOI: https://doi.org/10.69656/pjp.v20i3.1703

Basic coagulation parameters and platelet count among malaria patients attending at Addis Zemen Primary Hospital, Northwest Ethiopia.

Malaria is an intravascular parasitic-related blood disease that causes bleeding, coagulopathy, and thrombocytopenia. However, limited data shows the effect of Plasmodium species infection on basic coagulation parameters and platelet count. Thus, this study aimed to assess basic coagulation parameters and platelet count among malaria patients. A cross-sectional study was conducted among 240 study participants (120 cases and 120 controls) from June 1, 2021, to February 30, 2022. A convenient sampling technique was employed to select study participants. The blood sample was collected by a trained laboratory technologist for platelet counts, prothrombin time (PT), partial thromboplastin time (PTT), international normalization ratio (INR), blood film, and serological testing. The collected data were analyzed in SPSS version 23. Data were analyzed by the Mann-Whitney U test, Kruskal Wallis H, and Spearman's rank-order correlation tests. Descriptive findings were presented through median, tables, and chart. In all cases, a P-value < 0.05 was considered statistically significant. The percentage of mild, moderate, and high malaria parasitemia levels per microliter of blood was 21.7%, 20%, and 58.3%, respectively. The overall median malaria parasitemia was 10,304 per microliter of blood. Among malaria patients, 77.5%, 61.7%, and 51.7% had prolonged PT, INR, and APTT, respectively as compared to control. Moreover, 26.7% of Plasmodium-infected participants had mild thrombocytopenia as compared to the control group (P < 0.001). The value of PT, APTT, and INR were significantly elevated, whereas the level of platelet count was inversely reduced when the malaria parasitemia level increased as compared to controls (p < 0.001).

Unveiling the Unconventional: Exploring Atypical Manifestations of Scrub Typhus

Scrub typhus is a rickettsial illness caused by Orientia tsutsugamushi. It is a common cause of undifferentiated febrile illness, especially in the Indian subcontinent, usually with multiorgan involvement, though central nervous involvement is rare. Here, we demonstrate a case of a young female who presented with fever, headache, vomiting, and seizures. Her examination was remarkable for generalized blanchable macular rash, opsoclonus–myoclonus along with neck rigidity and mild epigastric tenderness. Contrast-enhanced magnetic resonance imaging brain was suggestive of leptomeningitis. She also had mild pancreatitis, transaminitis, thrombocytopenia, and transaminitis. Given the ongoing tropical fever burden in Northern India, further workup was done and enzyme-linked immunosorbent assay anti-scrub typhus immunoglobulin M came as positive. Doxycycline along with supportive treatment was started, and all signs and symptoms improved gradually.

Visceral leishmaniasis complicated with hemophagocytic lymphohistiocytosis and resistant to amphotericin B: a case report

IntroductionHemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein–Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000–90,000 new cases annually.Case presentationA 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis.ConclusionHemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases.

Clinical Presentations of Parvovirus B19: A Case Series.

Parvovirus B19 (PVB19) is a small, nonenveloped, single-stranded DNA virus commonly causing asymptomatic infections or mild, flu-like symptoms. In children, PVB19 can lead to various clinical conditions, including erythema infectiosum, arthropathy, transient aplastic crisis and papular-purpuric eruptions, among others. We present 3 pediatric cases treated at Luigi Sacco University Hospital in Milan, Italy, in March 2024, each demonstrating distinct manifestations of PVB19 infection. Case 1 involved a 7-year-old girl with a maculopapular rash and panniculitis-like symptoms. Case 2 described an 8-year-old boy with a maculopapular rash, vasculitis component and mild thrombocytopenia. Case 3 focused on a 7-year-old girl with petechial and purpuric eruptions and a mild decrease in platelets. Serological tests confirmed PVB19 infection in all cases. The discussed cases highlight the heterogeneous clinical spectrum of PVB19 infection and emphasize its potential to cause thrombocytopenia even in healthy children. The recent surge in PVB19 cases in Europe, aligned with known epidemiological cycles, underscores the importance of vigilance in diagnosis, particularly during peak seasons. Additionally, concerning the role of serological testing in the diagnostic process, the potential for cross-reactivity among viral antigens is pointed out. PVB19 is a common infection with a broad range of clinical presentations. Awareness of its potential complications, including thrombocytopenia, even in nonimmunocompromised children, is crucial. Moreover, understanding the epidemiological patterns of PVB19 can aid in anticipating and managing outbreaks, thus minimizing its impact on pediatric health.

Immature platelet fraction in patients diagnosed with COVID-19.

The recent pandemic caused by the newly identified virus, SARS-Cov-2 is associated with thromboembolic events. Patients infected with COVID-19 have been found to have thrombocytopenia. A decrease in platelet count may be caused by increased destruction and consumption of platelets or by decreased production of platelets in the bone marrow. Immature platelet fraction (IPF) is a new platelet parameter that is an indicator for peripheral destruction and consumption of platelets. To assess the immature platelet fraction (IPF) in patients infected with COVID-19. The present study is a retrospective study where secondary data obtained from previous laboratory records of COVID-positive patients admitted at a tertiary care hospital in Delhi from 4 January to 4 February 2022 was analyzed. Sixty-eight COVID-positive patients were included. Platelet parameters included from the automated hematology analyzer Mindray were platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and platelet large cell ratio (P-LCR). Data was analyzed using SPSS Version 25. A P value less than 0.05 was considered statistically significant. In the present study mild thrombocytopenia was noted in 40% of the patients infected with COVID-19 admitted to the hospital. The median platelet count in these patients was found to be 91,000/mm3 (64,000-1,31,000). Low platelet count was associated with a significantly higher IPF, MPV, PDW, P-LCR, and a significantly lower PCT as compared to patients infected with COVID-19 with normal platelet count. There was a significant increase in IPF with a decrease in platelet count (P value < 0.05). A significant increase in IPF was noted with an increase in MPV and P-LCR (P value < 0.05). The present study suggests that thrombocytopenia in patients infected with COVID-19 may probably be due to peripheral destruction and consumption of platelets.

Response, complications and risk of leukemic transformation of phosphorus-32 p treatment in philadelphia-negative chronic myeloproliferative syndromes

ObjectiveDescribe our experience in treatment with Phosphorus-32 P for refractory Philadelphia negative chronic myeloproliferative syndromes or with side effects to the usual treatment, its complications and risk of leukemic transformation. Material and methodsRetrospective descriptive study including 17 patients with a diagnosis of Philadelphia-negative chronic myeloproliferative syndrome treated with Phosphorus-32 P in our hospital from January 1985 to March 2017. Indications, response to treatment, as well as early and late complications have been analyzed. ResultsOf the 17 patients treated with 32 P (11 men, 6 women; mean age 79,8 years), 6 patients had Polycythemia Vera and 11 Essential Thrombocytosis. A single dose was administered in 9 of the subjects, the rest required two or more doses due to inadequate hematological response and/or relapse. The total dose range of Phosphorus-32 P administered was 116-951 MBq (median: 236 MBq). In 14 patients treated with Phosphorus-32 P, complete or partial response was achieved in hematimetry. In 11 patients, the response was complete, established as a platelet count < 400.000/mm3 in those diagnosed with Essential Thrombocythemia and a hematocrit < 45% in cases of Polycythemia Vera. The median follow-up of patients from the date of the first treatment of Phosphorus-32 P until study completion or death was 37 months (range: 5 - 230 months). Regarding early complications, 2 cases of anemia requiring blood transfusion were observed, and 1 case of mild thrombocytopenia. No leukemic transformation was identified. ConclusionsIn our experience, treatment with Phosphorus-32 P has been a useful therapeutic option in Philadelphia-negative chronic myeloproliferative syndromes in elderly patients who showed poor tolerance and/or resistance to first-line treatment. No leukemic transformation was identified.

Extramedullary Paravertebral Mass: An Unusual Presentation of Hairy Cell Leukaemia.

Hairy cell leukaemia (HCL) is an uncommon, indolent, B-cell, lymphoproliferative disorder typically involving peripheral blood, spleen and bone marrow. It is commonly presenting with pancytopenia, monocytopenia and massive splenomegaly, while accounting for 2% of lymphoid leukaemias. Cases of extranodal lesions caused by HCL are rare, although these have been reported. Here, we report a case of HCL presenting as a paravertebral mass without systemic involvement. A 58-year-old man was admitted to our hospital due to progressive difficulty walking for a month, without any other symptoms. Blood examination noted mild anaemia with Hb=12.6 g/dl and mild thrombocytopenia of 140,000/μl. Magnetic resonance imaging (MRI) and computed tomography (CT) imaging demonstrated a T6 posterior paravertebral mass lesion, extending into the spinal canal with metastatic bone lesions along the thoracic and lumbar spine. Further imaging study with CT indicated mild splenomegaly (13.4 cm) and an enlarged abdominal lymph node (3.5 cm) near celiac trifurcation. A core-needle biopsy from the paravertebral mass was performed. Results showed small-sized cells with round or oval nuclei, and pale cytoplasm with immunophenotype: B-cell origination with CD20+, Cyclin D1+, DBA.44+, Annexin+ and BRAF+, indicative of HCL. Hairy cell leukaemia (HCL) is relatively uncommon, accounting for 2% of all leukaemia cases.Extramedullary and skeletal involvement in HCL is rare and shares morphological characteristics with other peripheral small B-cell lymphoma neoplasms.Spine biopsy is essential for diagnosis in these cases, since it is always helpful to narrow the differential diagnosis.Correct diagnosis is essential for treatment of HCL and leads most patients to clinical remission and sometimes long-term cures.